Objective: Present study was aimed to evaluate the nonspecific hepatoprotective activity of HD-03/ES, a herbal combination, against experimental model of carbon tetrachloride (CCl4)-induced hepatic damage, and also free radical scavenging activity by using different in vitro antioxidant assay systems. Methods: The hepatoprotective activity of HD-03/ES was evaluated using an experimental model of CCl4-induced hepatic damage. The liver marker enzymes such as serum glutamate pyruvate transaminase (SGPT) and serum glutamate oxaloacetate transaminase (SGOT) were estimated apart from liver glycogen content and routine histopathological evaluation of liver samples. The free radical scavenging activity of HD-03/ES was evaluated by in vitro methods such as 2,2-Diphenyl-1-picrylhydrazyl (DPPH), reducing power (Fe3+-Fe2+) and oxygen radical absorbance capacity (ORAC) assays. Results: Administration of CCl4 to rats showed significant elevation of SGPT, SGOT and decrease in liver glycogen content. In addition, histopathology of the liver showed mild-to-moderate inflammatory reactions, severe degeneration and necrosis. Pretreatment with HD-03/ES (250, 500 and 1000 mg/kg, p.o.) showed significant and dose-dependent protection against CCl4-induced hepatic damage by normalizing serum SGPT and SGOT levels, and liver glycogen content. Furthermore, histopathology of HD-03/ES (500 and 1000 mg/kg) treated animals showed tendency toward normalization of cytoarchitecture of liver. In the antioxidant evaluation studies, HD-03/ES showed potent antioxidant activity by scavenging DPPH radicals (IC50 value = 499.4), exhibited reducing activity and also scavenging of peroxyl radical in the ORAC assay. Conclusion: These findings suggest that HD-03/ES formulation possesses significant hepatoprotective and antioxidant activities.